Mr. Grabski's research includes the identification of compounds against antibiotic resistant Pseudomonas aeruginosa and Staphylococcus aureus, as well as pharmacokinetics and pharmacodynamics of artemisinin using biochemical, biophysical, and structural bioinformatics.
In vitro and in silico identification of the interaction mechanism of antimalarial drug – artemisinin with human serum albumin and genomic DNA
Artemisinins are secondary metabolites of the medicinal plant Artemisia annua. Artemisinins have anti-inflammatory, anticarcinogenic, immunomodulatory, antimicrobial, anthelmintic, antiviral, antioxidant and other properties. Our preliminary reverse virtual screening demonstrated that the ligand-binding domain of the human glucocorticoid receptor is the optimal target for artemisinin. At the same time, the binding sites for artemisinin with the ligand-binding domain of the human glucocorticoid receptor coincide with those of dexamethasone. However, the pharmacokinetics, pharmacodynamics, and mechanisms of action of artemisinin are not well known. In this work, the interaction of artemisinin with human serum albumin (HSA) was studied both in vitro and in silico. Our results indicate that artemisinin leads to a decrease in optical absorption and quenching of fluorescence emission in dependence on its concentration and according to a single mechanism. The quenching of the fluorescence of HSA with artemisinin at different temperatures indicates the static nature of quenching. It is similar to the effect of dexamethasone. Energy transfer measurements have shown that the distance between Trp (donor) and ART (acceptor) was much smaller than the criterion value for the non-radiative energy transfer phenomenon. Artemisinin interacts with Drug site I on HSA and forms a hydrogen bond with arginine 218, which plays a crucial role in the binding of drugs, which includes thyroxine, warfarin, bilirubin, and cholesterol. We have shown that dexamethasone forms hydrogen bonds with Arg218, Arg222, and Val343. It should be noted that the many amino acids of HSA from IIA and IIIA subdomains that interact coincide for both artemisinin and dexamethasone. Retardation of the genomic DNA of sarcoma S-180 cells shows that artemisinin does not interact directly with DNA. We have also shown that artemisinin interacts with 1 site of the G-quadruplex structure. Artemisinin is associated with a groove located between G15 and G21.
